ABSTRACT An estimated 15,000 children under the age of five die every day. Primary causes of mortality include pneumonia and diarrhea, and nearly half of deaths are attributable to undernutrition. These syndromes all have available interventions to reduce mortality, however in many settings acutely ill children are not provided necessary evidence-based care. It is estimated that over half of child deaths are preventable with simple, existing, appropriately applied evidence-based interventions. Pediatric clinical treatment guidelines synthesize evidence to ensure that all children are treated with high quality care. Yet, fidelity to guidelines is variable and guideline knowledge exceeds adherence to recommendations. The objective of this study is to describe and evaluate the complex factors influencing pediatric guideline deviation in low-and-middle-income countries where most preventable pediatric deaths occur. This evidence is crucial for developing appropriate implementation strategies that can effectively improve pediatric quality of care in low-resource settings. This study involves both secondary data analysis and primary data collection and is nested within the Childhood Acute Illness and Nutrition (CHAIN) project, which has established a global research network to investigate risk factors for death in acutely ill children. This study will utilize existing CHAIN cohort data from nine health facilities in six countries to evaluate the frequency with which health providers deviate from established pediatric treatment guidelines, and factors that influence deviation. We will extract diagnostic and treatment criteria from each of the six country national guidelines, specifically for pneumonia, diarrhea, and severe acute malnutrition (SAM) sub-syndromes. We will map these criteria across CHAIN cohort data to identify the frequency with which providers deviate from the national guidelines on which they have been trained. We will additionally analyze CHAIN intake data to identify patient-level, provider-level, and contextual factors influencing provider deviation from guidelines. This will generate valuable information regarding multi-level factors that influence clinical decision making. Findings regarding the prevalence of guideline deviation across CHAIN will be used to identify the CHAIN site with the lowest observed guideline adherence across targeted syndromes. Primary qualitative data collection will take place in this site wherein health providers and supervisors will participate in focus group discussions (FGDs). Qualitative data collection and analysis will be guided by the Theoretical Domains Framework, an implementation science framework that can be applied to identify determinants of behavior. The combination of secondary data analysis and primary data collection will allow for triangulation between self-reported influences and observed influences of guideline deviation. This study is an innovative approach to rapidly understand the complex factors influencing quality of care for vulnerable children, providing an opportunity to develop optimized implementation strategies to improve guideline adherence and reduce preventable child mortality.